Multiple sclerosis is characterized morphologically by the key features
demyelination, inflammation, gliosis and axonal damage.

In recent years,
it has become more evident that axonal damage is the major morphological
substrate of permanent clinical disability.

In our study, we investigated
the occurrence of acute axonal damage determined by immunocytochemistry
for amyloid precursor protein (APP) which is produced in neurones and accumulates
at sites of recent axon transection or damage.

The numbers of APP-positive
axons in multiple sclerosis lesions were correlated with the disease duration
and course.

Most APP-positive axons were detected within the first year
after disease onset, but acute axonal damage was also detected to a minor
degree in lesions of patients with a disease duration of 10 years and more.

This effect was not due to the lack of active demyelinating lesions in
the chronic disease stage.

Late remyelinated lesions (so-called shadow
plaques) did not show signs of axon destruction.

The number of inflammatory
cells showed a decrease over time similar to that of the number of APP-positive
axons.

There was a significant correlation between the extent of axon damage
and the numbers of CD8-positive cytotoxic T cells and macrophages/microglia.

Our results indicate that a putative axon-protective treatment should start
as early as possible and include strategies preventing T cell/macrophage-mediated
axon destruction and leading to remyelination of axons.